Ingenol mebutate has the structure shown in Formula 1 and the following chemical names:    1) 2-Butenoic acid, 2-methyl (1aR,2S,5R,5aS,6S,8aS,9R,10aR)-1a,2,5,5a,6,9,10,10a-octahydro-5,5a-dihydroxy-4-(hydroxymethyl)-1,1,7,9-tetramethyl-11-oxo-1H-2,8a-methanocyclopenta[a]cyclopropa[e]cyclodecen-6-yl ester, (2Z)—    2) (1aR,2S,5R,5aS,6S,8aS,9R,10aR)-5,5a-dihydroxy-4-(hydroxymethyl)-1,1,7,9-tetramethyl-11-oxo-1a,2,5,5a,6,9,10,10a-octahydro-1H2,8a-methanocyclopenta[a]cyclopropa[e]cyclodecen-6-yl(2Z)-2-methylbut-2-enoate)

Ingenol mebutate (synonyms: PEP005, ingenol-3-angelate, CAS no. 75567-37-2) can be isolated from various Euphorbia species, and particularly from Euphorbia peplus and Euphorbia drummondii. Ingenol mebutate has the structure shown in Formula 1.
The preparation of Ingenol mebutate by extraction with 95% ethanol from the sap of Euphorbia peplus, Euphorbia hirta and/or Euphorbia drummondi; followed by chromatographic purification has been disclosed in EP1015413 B1, which is incorporated herein by reference in its entirety. Isolation from Euphorbia peplus has also been described by Hohmann et. al. Planta Med. 66, 3, (2000), which is incorporated herein by reference in its entirety. Other patent applications directed to ingenol mebutate and other pharmaceutically active ingenol derivatives include WO 2008/131491, WO 2007/068963, WO 2007/059584 and WO 2007/053912, each of which is incorporated herein by reference in its entirety.
Ingenol mebutate has been found to be highly toxic for skin cancer cells via rapid mitochondrial disruption and cell death by primary necrosis, whereas normal cells are less sensitive to ingenol mebutate.
Ingenol mebutate has been shown to be a potent anti-cancer drug and therapeutically effective in microgram quantities. Recent findings from a Phase III study evaluating ingenol mebutate in the treatment of actinic keratosis (AK), a common pre-cursor to skin cancer, were presented at the 68th Annual Meeting of the American Academy of Dermatology (AAD) (Scientific Session Poster Discussion: P105). Results from REGION-I of the study demonstrated that treatment with ingenol mebutate Gel once daily for 2 consecutive days (n=117) on non-head locations resulted in significant clearance of AK lesions when compared with the vehicle or placebo (n=118). The study showed a median reduction of about 66.7% in the number of AK lesions, (p<0.0001), a complete clearance rate of about 27.4% (p<0.0001) including on the extremely difficult-to-treat back of hand and arm locations, and a partial clearance rate of about 44.4% (p<0.0001).
Ingenol mebutate is commercially available in amorphous form, i.e., from Sigma-Aldrich. However, no crystalline form of ingenol mebutate has been reported.